The lithiation and subsequent alkylation of fluorene leads to various 9-alkyl-fluorenes in >95 % yields, for which lithiation and reaction with R2PCl (R=Cy, iPr, tBu) generates 9-alkyl, 9-PR2-fluorenes which constitute electron-rich and bulky phosphine ligands. With the synthesis of 37 different ligands of the fluorenyldialkylphosphine type the generality of the synthetic route as well as the high variability of this ligand family was demonstrated. The in-situ-formed palladium-phosphine complexes exhibit excellent catalytic activities in cross coupling reactions of the Sonogashira-, Suzuki-, and Buchwald-Hartwig amination type using aryl chlorides and aryl bromides as substrates. The high synthetic variability of the fluorene core of the ligands enables easy access to a doubly sulfonated and thus highly water soluble cross-coupling ligand termed cataCXium® FSulf. The use of Pd complexes of cataCXium® FSulf allows a sustainable, mild and efficient reaction protocol for Suzuki- and copper free Sonogashira- reactions using water as the only solvent. Using a rationally optimized water/n-butanol-mixture as reaction medium, the in situ formed Pd/cataCXium® FSulf complex displays an exceptional highly active catalyst for cross coupling reactions of heterocyclic substrates which are notorious for catalyst-deactivation. The robustness of this catalytic reaction protocol was demonstrated by coupling a broad scope of heterocyclic substrates including pyridines, quinones, indoles, triazines, anilines, purines, thiophenes or furanes by applying as little as 0.001-1 mol% catalyst loading. In order to improve the easy and inexpensive accessibility of this ligand family, successful upscaling studies were performed. Thus ligands of the cataCXium® F class are accessible high yield (>90 %) and high purity (>99 %) as their stable phosphonium salts in a multi kg scale.